Therapeutic intervention early in the course of schizophrenia may positively influence the outcome of this illness. The Environmental and Personal Indicators of Course in Schizophrenia (EPICS) treatment program at WPIC has developed a disorder-relevant rehabilitation of cognitive deficits (CET) found to be highly effective in chronic schizophrenic outpatients. Improvements in these cognitive deficits may reflect improved structural and functional integrity of the PFC and related structures. The Center for the Neuroscience of Mental Disorders (CNMD) at WPIC prospectively investigates PFC function in first-episode schizophrenia using structural and functional MRI and MRS. In this study, CNMD and EPICS investigators collaboratively seek to determine the efficacy of CET in ameliorating specific cognitive, structural and functional brain abnormalities in early course schizophrenia. We predict that CET will be more effective than enriched supportive psychotherapy (EST) in differentially improving behavioral and neurobiological dysfunctions in schizophrenia that compromise "executive" cognitive functions, specifically the structural and functional integrity of the PFC. We also predict that a relatively preserved PFC integrity will be associated with a better response to CET. A series of early course schizophrenic patients, stabilized on an atypical antipsychotic will be randomized to CET or EST. Cognitive and functional outcomes will be assessed before, and following 1 and 2 years of psychosocial treatment and maintenance antipsychotic treatment. In a subset of these patients, an integrated neuroimaging study will be conducted before and one year after the CET or EST. If successful, the study will provide the first evidence of neurobiological remediation, and possible mechanisms and site(s) of action, for cognitive rehabilitation in early schizophrenia. An understanding of the cerebral correlates of improvement (or lack thereof) in cognition and behavior might guide development of future cognitive rehabilitation strategies for schizophrenia.